Long-Term Inhaled Corticosteroid Use and the Risk of Open-Angle Glaucoma in Patients with Chronic Obstructive Pulmonary Disease

Inès Ben Ghezala,1– 4 Sophie Dell’Aniello,4 Pierre Ernst,4,5 Samy Suissa1,4,51Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; 2Department of Ophthalmology, Université Bourgogne Europe-CHU Dijon, Dijon, France; 3Clinical Investigation Center, Inserm CIC 1432, Clinical Epidemiology/Clinical Trials Unit, Université Bourgogne Europe-CHU Dijon, Dijon, France; 4Center for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital University Health Centre, Montreal, QC, Canada; 5Department of Medicine, McGill University, Montreal, QC, CanadaCorrespondence: Samy Suissa, Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital University health Centre, 3755 Chemin de la Côte Sainte-Catherine, Montreal, QC, H3T 1E2, Canada, Email [email protected]: The question of whether inhaled corticosteroids (ICS) increase the risk of open-angle glaucoma (OAG) has produced conflicting data on short-term effects, but no study has evaluated their long-term effects. We assessed whether long-term cumulative ICS use is associated with an increased risk of incident OAG among patients with chronic obstructive pulmonary disease (COPD).Patients and Methods: The United Kingdom Clinical Practice Research Datalink was used to form a cohort of patients with COPD, aged 40 years or more, who initiated an inhaled maintenance treatment, between September 2013 and March 2021. Subjects were followed until the occurrence of the first OAG diagnosis. Using a nested case-control design, each OAG case was matched with up to 100 concurrently glaucoma-free controls using risk-set sampling. Conditional logistic regression was used to compute the adjusted odds ratio of incident OAG associated with cumulative ICS exposure, as an estimate of the hazard ratio (HR) and its 95% confidence interval (CI).Results: The COPD cohort included 84,564 subjects, with 732 developing OAG (incidence rate 2.64 per 1000 person-years) and 56% having used an ICS since cohort entry. The adjusted HR of OAG associated with any ICS use since cohort entry, compared with non-use, was 1.14 (95% CI, 0.94– 1.38). The HR was 1.11 (95% CI, 0.83– 1.48) for total cumulative dose ≥ 365 mg and 1.23 (95% CI, 0.90– 1.68) for over 3 years since ICS initiation.Conclusion: This large cohort study did not observe a statistically significant increase in the risk of OAG with ICS use, including long-term use and higher cumulative doses, among patients with COPD.Keywords: glucocorticoids, respiratory diseases, open-angle glaucoma, clinical practice research datalink, CPRD, pharmacoepidemiology, drug safety